There is a body of epidemiologic evidence that has associated the birth of children with Down's syndrome or with other trisomies with the presence of thyroid antibodies in the serum of those children's parents. Cases for such studies were selected from children or adults with the syndromes who had survived the earliest years of life. If thyroid antibodies are a risk factor for chromosomal non-disjunction, then those antibodies should be present in a parent at the time of conception; otherwise the association could be due to selection bias for survivors whose altered immune system could be protective. We will test the hypothesis of an association of thyroid antibodies with trisomy births in a case-control study in which all cases and controls were ascertained at birth and all parental sera were drawn at the beginning of the pregnancy and stored for future research. 115 cases have been identified from the records of two large longitudinal studies, the Child Health and Development Study (CHDS) and the Collaborative Perinatal Project (CPP), with some 20,000 and 50,000 births respectively. Three controls per case will be selected from the same populations and matched for age and race of the mother and the father. Parental sera will be tested for thyroid antibodies. If this association is verified, it could have important public health implications because, at this time, there are no known risk factors other than age for the identification of mothers at risk of a trisomy birth. Although the incidence of DS is 10 to 100 times greater in women 35 to 45 years of age, the majority of DS are born to younger mothers for whom, as a group, amniocentesis would not be cost or risk effective. A test for thyroid antibodies is inexpensive and without risk to the mother-child pair. Mothers who were positive could then be tested by other means such as amniocentesis. This study design offers the unique opportunity to test this important hypothesis at a minimum of cost because the needed records and bloods are already available for analysis.